S-Adenosylmethionine biosynthesis pathway

The **S-Adenosylmethioninase pathway** is more accurately referred to as the **S-Adenosylmethionine biosynthesis or methionine/SAM cycle**. This metabolic route centers on the synthesis and utilization of *S*-adenosyl-L-methionine (SAM), a universal methyl group donor involved in numerous biological processes including DNA/RNA/protein/lipid methylation and epigenetic regulation. The core enzyme responsible for SAM production is *S*-adenosylmethionine synthetase (also called methionine adenosyltransferase), which catalyzes the reaction between ATP and L-methionine to form SAM[1][3]. Downstream enzymes use SAM as a cofactor for transmethylation reactions; after donating its methyl group, it is converted into *S*-adenosylhomocysteine. Disruption of this pathway—such as by inhibiting key enzymes—can be lethal to certain pathogens like *Mycobacterium tuberculosis*, making it an attractive target for antimicrobial drug development due to its multitarget inhibition effect leading to rapid cell death without resistance emergence[2]. In humans, altered function or dysregulation has been implicated in cancer progression, neurodegeneration, liver diseases such as cirrhosis/hepatitis, psychiatric conditions like depression,[4] and other pathologies. Therapeutically relevant drugs include **Ademetionine** (*SAMe*), used particularly in Europe for treating depression and liver disorders. However, safety concerns exist regarding systemic effects from altering global cellular methylation capacity or from direct adverse effects such as CNS depression when administered exogenously[4]. Note: The term "S-Adenosylmethioninase" does not refer specifically to any single enzyme but rather seems intended here as shorthand for the broader metabolic/methyltransferase system involving S-Adenosyl-L-methionine. Therefore, this entry is not a canonical molecular target but rather describes an entire metabolic/enzymatic process.

Other names

Methionine/S-adenosylmethionine pathwaySAM cycleMethionine cycleS-Adenosyl-L-methionine pathway

Inhibition of enzymes in the methionine/SAM biosynthetic pathway leads to depletion of essential methyl donors and disruption of vital cellular processes[2]